Background Type 2 diabetes mellitus (T2DM) is a condition characterized by insulin resistance and progressive failure of the insulin-secreting beta-cells. Based on studies in small cohorts of young patients (especially Pima Indian offspring), we know that individuals with childhood onset T2DM are at very high risk for diabetes-related morbidity and mortality, due to a longer life-time duration of diabetes, as well as possible faster progression of beta-cell failure. Based on the currently largest available interventional trial, the TODAY study (Treatment Options for Diabetes in Adolescents and Youth), we know that standard medical treatments (e.g., diet, exercise, metformin) are prone to fail in most patients. Our study objectives are to acquire data on the natural history of T2DM in youth. Measurements will include indices of beta-cell function, body composition, cardiovascular disease risk factors, gut hormones, adipokines, and psychological well-being. These data will be compared to findings in non-diabetic volunteers who are lean or overweight/obese. The study will also allow us to collaborate with other investigators in order to investigate factors (e.g. body composition changes, effect of life-style changes (such as sleep)) that determine the progression to and outcome of type 2 diabetes. One specific goal is to investigate the effects of a new class of drugs, sodium glucose co-transporter 2 (SGLT2) inhibitors, on bone health and to learn more about their safety profile as compared to other hypoglycemic agents. Presently we are recruiting healthy individuals in order to elucidate the underlying mechanisms of drug action on bone metabolism. In the future, we are planning to widen the spectrum of study participants and include patients with diabetes and individuals at heightened risk for bone fractures. A third objective is to continue clinical follow-up of patients with Type 1 Diabetes (e.g., after islet transplantation and after having received low dose oral interferon alpha or exenatide). We are also analyzing and sharing stored samples (e.g., serum and plasma)in order to learn about predictors of beta cell loss.